Genetic Therapy for Brain Tumors and Cancers
Brain Tumors Very little is known about what causes brain tumors and there are only a few known risk factors that researchers have established. Children who have had exposure to radiation to the head have a higher risk of developing brain tumors as adults. Furthermore, people with rare genetic conditions, such as neurofibrosis, are prone to brain tumors. Age is also a risk factor and the rate of people diagnosed over the age of 65 is four times higher that that of younger people. There are about 35,000 new primary brain tumors diagnosed every year. Primary brain tumors form in the brain and are not always cancerous. Since they are benign, they generally do not spread to surrounding tissues. However, sometimes they can become serious and even life threatening. It was estimated that there would be about 23,380 new cases of brain cancer by 2014. What is a tumor? A tumor is a mass of tissue that is formed when abnormal cells accumulate. Normally, body cells age, die and are replaced with new cells. However, with cancer and other tumors, there is a disruption in the cycle, which allows tumors to grow even if the body does not require them. Furthermore, the do not die, so they continue to grow and more cells are added. Gene Therapy Using Intra-Tumoral Transduction with HS-tk Gene and Intravenous GCV Malignant brain tumors are responsible for significant morbidity and mortality in child and adult populations, and they are a huge challenge because of their poor outcome despite radical surgery, high dose radiotherapy and chemotherapy. Most of the time, survival of patients from the time of diagnosis is associated with a few months. Recurrence after treatment could bring life expectancy down to a few weeks. A new genetic therapy approach was developed to treat brain tumors in hopes of increasing the life expectancy of patients with malignant tumors. The new approach involves the use of recombinant DNA technology to transfer a sensitivity gene into a brain tumor. A cell line that is actively producing a retroviral vector with the gene conferring drug sensitivity is directly injected into the tumor. In an experiment, a mouse was the retroviral vector that was genetically engineered, and its genes were replaced with new genes. These vectors infect mammalian cells and incorporate new genetic material into the infected host. NIH 3T3 is the producer cell. It is genetically engineered to continuously create retroviral vectors. When the new gene is incorporated into the genome of the tumor cells, it begins to express a new protein that the new gene is responsible for encoding. This protein is the herpes simplex virus enzyme thymidine kinase (HS-tk). It sensitizes the tumor cells to ganciclovir (GCV), an antiviral drug. GCV is the natural substrate for HS-tk. GCM induces an enzymatic process that causes any cells that express the HS-tk gene to die, thereby killing tumor cells. HS-tk is usually present in mammalian cells. It also has a lof affinity for GCV. This means that researchers do not observe the systemic toxicity of the mechanism and the features of the gene transfer are unique. For example, the retroviral-vectors integrate and express their genes only in cells that are actively synthesizing DNA. Since the normal brain tissue surrounding the brain does not proliferate, this portion remains insensitive to GCV. Furthermore, the host immune system kills the transduced tumor cells and retroviral vector producing cells. This technique aims to treat malignant and cancerous tumors via in-vivo genetic manipulation of the tumor’s genome itself. This works because murine retroviral vectors are capable of infecting a wide variety of proliferating mammalian cell types but not non-proliferating cell types. They can assist in selectively introducing genes into growing tumors. The results of the study revealed that 40-80% of the tumor cells in surrounding normal brain tissue were transducted. Additionally, there was no toxicity in mice, rats and non-human primates. This suggests that the direct injection of the G1TkSvNa producer cell line into the tumors will regress with GCV therapy. References http://www.webmd.com/cancer/brain-cancer/brain-tumors-in-adults http://www.ncbi.nlm.nih.gov/pubmed/8384892 http://online.liebertpub.com/doi/abs/10.1089/hum.1993.4.1-39